JP2013256475A - グリチルリチン酸含有水性眼科組成物 - Google Patents
グリチルリチン酸含有水性眼科組成物 Download PDFInfo
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- JP2013256475A JP2013256475A JP2012134601A JP2012134601A JP2013256475A JP 2013256475 A JP2013256475 A JP 2013256475A JP 2012134601 A JP2012134601 A JP 2012134601A JP 2012134601 A JP2012134601 A JP 2012134601A JP 2013256475 A JP2013256475 A JP 2013256475A
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- Prior art keywords
- ophthalmic composition
- aqueous ophthalmic
- castor oil
- component
- present
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 229
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 title claims abstract description 48
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 239000001685 glycyrrhizic acid Substances 0.000 title claims abstract description 48
- 229960004949 glycyrrhizic acid Drugs 0.000 title claims abstract description 48
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 235000019410 glycyrrhizin Nutrition 0.000 title claims abstract description 48
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 title claims abstract description 48
- -1 polyoxyethylene Polymers 0.000 claims abstract description 109
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- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims abstract description 78
- 150000003839 salts Chemical class 0.000 claims abstract description 61
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- 238000000034 method Methods 0.000 claims description 50
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
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- 239000004698 Polyethylene Substances 0.000 description 6
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- 239000002253 acid Substances 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 6
- 239000006172 buffering agent Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000012790 confirmation Methods 0.000 description 6
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- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 5
- 239000005977 Ethylene Chemical group 0.000 description 5
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- 239000004327 boric acid Substances 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
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- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical group [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 229920001214 Polysorbate 60 Polymers 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
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- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 235000004443 Ricinus communis Nutrition 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 229920001400 block copolymer Polymers 0.000 description 3
- 229910021538 borax Inorganic materials 0.000 description 3
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
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- 235000011187 glycerol Nutrition 0.000 description 3
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- 229920001684 low density polyethylene Polymers 0.000 description 3
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- 238000005259 measurement Methods 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 3
- 229920001992 poloxamer 407 Polymers 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
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- 150000005846 sugar alcohols Polymers 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
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- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 244000303040 Glycyrrhiza glabra Species 0.000 description 2
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 2
- FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- 229910019142 PO4 Inorganic materials 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
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- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 2
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- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
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- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
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- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 2
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- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 description 2
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- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
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- BJORNXNYWNIWEY-UHFFFAOYSA-N tetrahydrozoline hydrochloride Chemical compound Cl.N1CCN=C1C1C2=CC=CC=C2CCC1 BJORNXNYWNIWEY-UHFFFAOYSA-N 0.000 description 1
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- ZXHXYXSTAYNRLQ-DWJAGBRCSA-K tripotassium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4s,5s,6s)-2-[[(3s,4ar,6ar,6bs,8as,11s,12ar,14ar,14bs)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-6-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-3,4, Chemical compound [K+].[K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C([O-])=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O ZXHXYXSTAYNRLQ-DWJAGBRCSA-K 0.000 description 1
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Abstract
【解決手段】(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と、(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を含む水性眼科組成物においては、(A)成分の熱分解及び光分解が抑制され、(B)成分を含む水性眼科組成物における消泡時間が短縮される。
【選択図】なし
Description
項1-1.(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と、(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を含む水性眼科組成物。
項1-2. (B)成分が、酸化エチレンの平均付加モル数が2〜12であるポリオキシエチレンヒマシ油である、項1-1に記載の水性眼科組成物。
項1-3.水性眼科組成物の総量を基準として、(A) 成分の総含有量が0.0005〜2w/v%である、項1-1又は1-2に記載の水性眼科組成物。
項1-4.水性眼科組成物の総量を基準として、(B)成分の総含有量が0.0005〜5w/v%である、項1-1乃至1-3のいずれかに記載の水性眼科組成物。
項1-5.(A)成分の総含有量1重量部に対して、(B)成分の総含有量が0.0002〜10000重量部である、項1-1乃至1-4のいずれかに記載の水性眼科組成物。
項1-6.(A)成分の総含有量1重量部に対して、(B)成分の総含有量が0.05〜50重量部である、項1-1乃至1-5のいずれかに記載の水性眼科組成物。
項1-7.更に緩衝剤を含有する、項1-1乃至1-6のいずれかに記載の水性眼科組成物。
項1-8.緩衝剤がホウ酸緩衝剤である、項1-7に記載の水性眼科組成物。
項1-9.水性眼科組成物の総量を基準として、緩衝剤の総含有量が0.01〜10w/v%である、項1-7又は1-8に記載の水性眼科組成物。
項1-10. 更に(B)成分以外の非イオン性界面活性剤を含有する、項1-1乃至1-9のいずれかに記載の水性眼科組成物。
項1-11.(B)成分以外の非イオン性界面活性剤が、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、酸化エチレンの平均付加モル数が30を上回るポリオキシエチレンヒマシ油、及びポリオキシエチレン・ポリオキシプロピレン・ブロックコポリマーからなる群より選択される少なくとも1種である、項1-10に記載の水性眼科組成物。
項1-12.水性眼科組成物の総量を基準として、(B)成分以外の非イオン性界面活性剤の総含有量が0.001〜3w/v%である、項1-10又は1-11に記載の水性眼科組成物。
項1-13.ポリエチレンテレフタレート製容器に充填されてなる、項1-1乃至1-12のいずれかに記載の水性眼科組成物。
項1-14.ポリエチレン製ノズルが装着された容器に充填されてなる、項1-1乃至1-13のいずれかに記載の水性眼科組成物。
項1-15.点眼剤である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-16.洗眼剤である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-17.コンタクトレンズ装着液である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項1-18.コンタクトレンズケア用剤である項1-1乃至1-14のいずれかに記載の水性眼科組成物。
項2. (A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種を含有する水性眼科組成物に、(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することを含む、該水性眼科組成物における熱安定性を向上させる方法。
項3. 水性眼科組成物中に、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することを含む、該水性眼科組成物における熱安定性を向上させる方法。
項4. (A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種を含有する水性眼科組成物に、(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することを含む、該水性眼科組成物における光安定性を向上させる方法。項5. 水性眼科組成物中に、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することを含む、該水性眼科組成物における光安定性を向上させる方法。
項6.(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と、(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を、水性眼科組成物に配合することを含む、該水性眼科組成物における消泡時間を短縮させる方法。
項7.(B) 酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を含有する水性眼科組成物に、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種を配合することを含む、該水性眼科組成物における消泡時間を短縮させる方法。
項8.(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と、(B) 酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を、水性眼科組成物に配合することを含む、該水性眼科組成物における使用時の滴下量のバラツキを抑制する方法。
項9. 水性眼科組成物の製造のための、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油の使用。
項10. 水性眼科組成物が、上記項1-1乃至1-18のいずれかに記載の組成物である、項9に記載の使用。
項11. 水性眼科組成物としての、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を含む組成物の使用。
項12. 組成物が、上記項1-1乃至1-18のいずれかに記載の組成物である、項11に記載の使用。
項13. 水性眼科組成物としての使用のための、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を含む組成物。
項14. 上記項1-1乃至1-18のいずれかに記載されたものである、項13に記載の組成物。
項15. 水を含む担体に、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を添加することを含む、水性眼科組成物の製造方法。
項16. 水性眼科組成物が、上記項1-1乃至1-18のいずれかに記載の組成物である、項15に記載の製造方法。
(1)本発明によれば、グリチルリチン酸及び/又はその塩を含有する水性眼科組成物において、保存時や光を晒した場合に生じ易いグリチルリチン酸及びその塩の熱分解及び光分解を抑制することができる。よって、本発明の水性眼科組成物は、安全性や品質を低下させることなく、グリチルリチン酸及び/又はその塩の有する優れた性能を長期間安定して発揮することができる。
(2)本発明によれば、ポリオキシエチレンヒマシ油を含有する水性眼科組成物における消泡時間を短縮させることができる。その結果、水性眼科組成物の製造時の溶解確認又は異物確認を短時間で行うことが可能となり、製造効率を改善することができる。更に、消泡時間が短縮されることにより、滴下量のバラツキをも抑制することができる。
本発明の水性眼科組成物は、グリチルリチン酸及びその塩からなる群から選択される少なくとも一種((A)成分)を含有するものである。これを、後述する酸化エチレンの平均付加モル数が2〜30のポリオキシエチレンヒマシ油と併用することによって、上記した本発明の優れた効果が発揮される。
前述した通り、水性眼科組成物中に、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と共に、(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することによって、(A)成分を含有する水性眼科組成物を加熱した状態で保存した場合に生じ易い(A)成分の熱分解を抑制することができる。
従って、本発明は、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種を含有する水性眼科組成物に、(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することを含む、該水性眼科組成物における熱安定性を向上させる方法を提供するものである。
前述した通り、水性眼科組成物中に、(A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と共に、(B)酸化エチレンの平均付加モル数が2〜30であるポリオキシエチレンヒマシ油を配合することによって、該水性眼科組成物に含まれる(A)成分の光分解を抑制することができる。
前述したように、本発明の水性眼科組成物では、(A)成分及び(B)成分を併用することによって、(B)成分を含有する水性眼科組成物における消泡時間を短縮させることができ、更に、その結果、使用時の滴下量のバラツキを抑制することができる。
下記表1に示される水性眼科組成物を常法により調製し、熱安定性を評価した。グリチルリチン酸二カリウムとしては、WAKO製のものを用いた。なお、ポリオキシエチレンヒマシ油10及びポリオキシエチレンヒマシ油35としては、医薬品添加物規格2003のポリオキシエチレンヒマシ油の規格に適合するものであって、酸化エチレンの平均付加モル数が10と35のものを用いた。
下記表2に示す組成の水性眼科組成物を常法により調製し、光安定性を評価した。なお、グリチルリチン酸二カリウム、ポリオキシエチレンヒマシ油10、及びポリオキシエチレンヒマシ油35としては、試験例1と同じものを用いた。
下記表3に示す組成の水性眼科組成物を常法により調製し、消泡時間を評価した。なお、グリチルリチン酸二カリウム及びポリオキシエチレンヒマシ油10としては、試験例1と同じものを用いた。
表4及び表5に記載の処方で、常法により、点眼剤(製剤例1〜10)を調製する。
Claims (5)
- (A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種と、(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を含む水性眼科組成物。
- (B)成分が、酸化エチレンの平均付加モル数が2〜12であるポリオキシエチレンヒマシ油である、請求項1に記載の水性眼科組成物。
- (A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を水性眼科組成物に配合することを含む、該水性眼科組成物における熱安定性を向上させる方法。
- (A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を水性眼科組成物に配合することを含む、該水性眼科組成物における光安定性を向上させる方法。
- (A) グリチルリチン酸及びその塩からなる群から選択される少なくとも一種、並びに(B) 酸化エチレンの平均付加モル数が2〜30モルであるポリオキシエチレンヒマシ油を水性眼科組成物に配合することを含む、該水性眼科組成物における消泡時間を短縮させる方法。
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